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Spotting immunodeficiency in the pediatric dermatology clinic
SEATTLE – Immunodeficiency in children can look much like eczematous dermatitis. Be aware of this potential diagnosis.
“Although it is important to know these are extremely rare conditions, you don’t want to miss them because you can literally change that child’s life,” Markus Boos, MD, an assistant professor of pediatrics at the University of Washington, Seattle, said in an interview at the annual Coastal Dermatology Symposium.
He outlined some key clinical features and patient history that can raise a potential red flag.
“ and you really spend time looking at the morphology and distribution of the rash,” Dr. Boos said.
The distribution of the rash also can be distinctive. For example, hyper-IgE syndrome shows up as little red pus bumps that are widespread, but specifically occur on the face and other areas that usually aren’t affected eczematous dermatitis. “You should really focus on that, and not just assume that because something [like eczematous dermatitis] is common, everything has to be that,” Dr. Boos said at the meeting, which was jointly presented by the University of Louisville and Global Academy for Medical Education.
He also warned about a false positive. You may be alerted to high eosinophil and high IgE levels determined by a primary care physician’s tests, but these aren’t necessarily a strong indicator of hyper-IgE syndrome, he said. “Many inflammatory conditions in children have high levels of both those, so they aren’t a distinguishing feature of any one of them. You can reassure a family that the child doesn’t necessarily have hyper-IgE syndrome. There’s this leap [people take] because it sounds like the name, but it’s not a very specific marker of that particular condition.”
Patient history of an immunodeficiency patient in general obviously can include a history of infections, although a high rate of ear infections is pretty typical among children. The key is to ask yourself: “At what point does it seem like something that is beyond normal?” Dr. Boos said. Infections that required hospitalizations or were invasive or required antibiotics all are potential clues. Other factors to consider include growth and development issues such as frequent diarrhea or failure to thrive, or family members with frequent infections or who died prematurely.
Hyper-IgE patients also may have a prominent forehead and chin, deep-set eyes, broad nose, thickened facial skin, or a high arched palate. These physical features become more prominent by adolescence. For a reference for physical features go to https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/hyper-ige-syndrome.
Clinical features of various immunodeficiencies include the following:
- Papulopustular eruption with frequent infections and musculoskeletal changes. This presentation is suggestive of autosomal dominant hyper-IgE syndrome. These children have a “heterozygous mutation in the gene encoding the transcription factor STAT3,” according to the Immune Deficiency Foundation.
- Severe atopy with extensive warts/molluscum/herpes simplex virus. This presentation is suggestive of autosomal recessive hyper-IgE syndrome. These children have “mutations and deletions in the DOCK8 gene,” the Immune Deficiency Foundation asserts.
- Diffusely red baby. Consider immunodeficiency if the patient also has experienced failure to thrive and/or diarrhea, or has a history of infection. High IgE levels are not a strong signal of hyper-IgE syndrome.
- Severe eczematous (or psoriasiform) dermatitis with chronic diarrhea, failure to thrive, and diabetes or hypothyroidism. This presentation is suggestive of IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked).
- Atopic dermatitis with bloody diarrhea, thrombocytopenia, recurrent ear infections. This presentation is indicative of Wiskott-Aldrich syndrome.
Dr. Boos is personally familiar with primary immunodeficiencies because he works closely with an immunology clinic, which also means he has a lot of support. Most clinicians diagnosing these patients don’t. If you find yourself with a case, “call in the troops,” he advised. You should be connected to a rheumatologist when there’s evidence of autoimmune disease, and hematologists or oncologists for the treatment, which requires a bone marrow transplant in the case of autosomal recessive hyper-IgE syndrome. Otherwise treatment is largely supportive for this immunodeficiency.
Having that network can be invaluable in managing what can be a very complicated patient. “If you ever feel uncomfortable making a decision about their care, discussing it with those other providers can give you some peace of mind,” he said.
Dr. Boos disclosed that he is a clinical researcher for Regeneron. This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – Immunodeficiency in children can look much like eczematous dermatitis. Be aware of this potential diagnosis.
“Although it is important to know these are extremely rare conditions, you don’t want to miss them because you can literally change that child’s life,” Markus Boos, MD, an assistant professor of pediatrics at the University of Washington, Seattle, said in an interview at the annual Coastal Dermatology Symposium.
He outlined some key clinical features and patient history that can raise a potential red flag.
“ and you really spend time looking at the morphology and distribution of the rash,” Dr. Boos said.
The distribution of the rash also can be distinctive. For example, hyper-IgE syndrome shows up as little red pus bumps that are widespread, but specifically occur on the face and other areas that usually aren’t affected eczematous dermatitis. “You should really focus on that, and not just assume that because something [like eczematous dermatitis] is common, everything has to be that,” Dr. Boos said at the meeting, which was jointly presented by the University of Louisville and Global Academy for Medical Education.
He also warned about a false positive. You may be alerted to high eosinophil and high IgE levels determined by a primary care physician’s tests, but these aren’t necessarily a strong indicator of hyper-IgE syndrome, he said. “Many inflammatory conditions in children have high levels of both those, so they aren’t a distinguishing feature of any one of them. You can reassure a family that the child doesn’t necessarily have hyper-IgE syndrome. There’s this leap [people take] because it sounds like the name, but it’s not a very specific marker of that particular condition.”
Patient history of an immunodeficiency patient in general obviously can include a history of infections, although a high rate of ear infections is pretty typical among children. The key is to ask yourself: “At what point does it seem like something that is beyond normal?” Dr. Boos said. Infections that required hospitalizations or were invasive or required antibiotics all are potential clues. Other factors to consider include growth and development issues such as frequent diarrhea or failure to thrive, or family members with frequent infections or who died prematurely.
Hyper-IgE patients also may have a prominent forehead and chin, deep-set eyes, broad nose, thickened facial skin, or a high arched palate. These physical features become more prominent by adolescence. For a reference for physical features go to https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/hyper-ige-syndrome.
Clinical features of various immunodeficiencies include the following:
- Papulopustular eruption with frequent infections and musculoskeletal changes. This presentation is suggestive of autosomal dominant hyper-IgE syndrome. These children have a “heterozygous mutation in the gene encoding the transcription factor STAT3,” according to the Immune Deficiency Foundation.
- Severe atopy with extensive warts/molluscum/herpes simplex virus. This presentation is suggestive of autosomal recessive hyper-IgE syndrome. These children have “mutations and deletions in the DOCK8 gene,” the Immune Deficiency Foundation asserts.
- Diffusely red baby. Consider immunodeficiency if the patient also has experienced failure to thrive and/or diarrhea, or has a history of infection. High IgE levels are not a strong signal of hyper-IgE syndrome.
- Severe eczematous (or psoriasiform) dermatitis with chronic diarrhea, failure to thrive, and diabetes or hypothyroidism. This presentation is suggestive of IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked).
- Atopic dermatitis with bloody diarrhea, thrombocytopenia, recurrent ear infections. This presentation is indicative of Wiskott-Aldrich syndrome.
Dr. Boos is personally familiar with primary immunodeficiencies because he works closely with an immunology clinic, which also means he has a lot of support. Most clinicians diagnosing these patients don’t. If you find yourself with a case, “call in the troops,” he advised. You should be connected to a rheumatologist when there’s evidence of autoimmune disease, and hematologists or oncologists for the treatment, which requires a bone marrow transplant in the case of autosomal recessive hyper-IgE syndrome. Otherwise treatment is largely supportive for this immunodeficiency.
Having that network can be invaluable in managing what can be a very complicated patient. “If you ever feel uncomfortable making a decision about their care, discussing it with those other providers can give you some peace of mind,” he said.
Dr. Boos disclosed that he is a clinical researcher for Regeneron. This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – Immunodeficiency in children can look much like eczematous dermatitis. Be aware of this potential diagnosis.
“Although it is important to know these are extremely rare conditions, you don’t want to miss them because you can literally change that child’s life,” Markus Boos, MD, an assistant professor of pediatrics at the University of Washington, Seattle, said in an interview at the annual Coastal Dermatology Symposium.
He outlined some key clinical features and patient history that can raise a potential red flag.
“ and you really spend time looking at the morphology and distribution of the rash,” Dr. Boos said.
The distribution of the rash also can be distinctive. For example, hyper-IgE syndrome shows up as little red pus bumps that are widespread, but specifically occur on the face and other areas that usually aren’t affected eczematous dermatitis. “You should really focus on that, and not just assume that because something [like eczematous dermatitis] is common, everything has to be that,” Dr. Boos said at the meeting, which was jointly presented by the University of Louisville and Global Academy for Medical Education.
He also warned about a false positive. You may be alerted to high eosinophil and high IgE levels determined by a primary care physician’s tests, but these aren’t necessarily a strong indicator of hyper-IgE syndrome, he said. “Many inflammatory conditions in children have high levels of both those, so they aren’t a distinguishing feature of any one of them. You can reassure a family that the child doesn’t necessarily have hyper-IgE syndrome. There’s this leap [people take] because it sounds like the name, but it’s not a very specific marker of that particular condition.”
Patient history of an immunodeficiency patient in general obviously can include a history of infections, although a high rate of ear infections is pretty typical among children. The key is to ask yourself: “At what point does it seem like something that is beyond normal?” Dr. Boos said. Infections that required hospitalizations or were invasive or required antibiotics all are potential clues. Other factors to consider include growth and development issues such as frequent diarrhea or failure to thrive, or family members with frequent infections or who died prematurely.
Hyper-IgE patients also may have a prominent forehead and chin, deep-set eyes, broad nose, thickened facial skin, or a high arched palate. These physical features become more prominent by adolescence. For a reference for physical features go to https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/hyper-ige-syndrome.
Clinical features of various immunodeficiencies include the following:
- Papulopustular eruption with frequent infections and musculoskeletal changes. This presentation is suggestive of autosomal dominant hyper-IgE syndrome. These children have a “heterozygous mutation in the gene encoding the transcription factor STAT3,” according to the Immune Deficiency Foundation.
- Severe atopy with extensive warts/molluscum/herpes simplex virus. This presentation is suggestive of autosomal recessive hyper-IgE syndrome. These children have “mutations and deletions in the DOCK8 gene,” the Immune Deficiency Foundation asserts.
- Diffusely red baby. Consider immunodeficiency if the patient also has experienced failure to thrive and/or diarrhea, or has a history of infection. High IgE levels are not a strong signal of hyper-IgE syndrome.
- Severe eczematous (or psoriasiform) dermatitis with chronic diarrhea, failure to thrive, and diabetes or hypothyroidism. This presentation is suggestive of IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked).
- Atopic dermatitis with bloody diarrhea, thrombocytopenia, recurrent ear infections. This presentation is indicative of Wiskott-Aldrich syndrome.
Dr. Boos is personally familiar with primary immunodeficiencies because he works closely with an immunology clinic, which also means he has a lot of support. Most clinicians diagnosing these patients don’t. If you find yourself with a case, “call in the troops,” he advised. You should be connected to a rheumatologist when there’s evidence of autoimmune disease, and hematologists or oncologists for the treatment, which requires a bone marrow transplant in the case of autosomal recessive hyper-IgE syndrome. Otherwise treatment is largely supportive for this immunodeficiency.
Having that network can be invaluable in managing what can be a very complicated patient. “If you ever feel uncomfortable making a decision about their care, discussing it with those other providers can give you some peace of mind,” he said.
Dr. Boos disclosed that he is a clinical researcher for Regeneron. This publication and Global Academy for Medical Education are owned by the same parent company.
EXPERT ANALYSIS FROM COASTAL DERM
Rituximab bests mycophenolate in pemphigus vulgaris
MADRID – Pascal Joly, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Not only did rituximab prove superior in terms of efficacy in the PEMPHIX trial, with a five times greater likelihood of achieving a complete remission lasting for at least 16 weeks while off oral corticosteroids than with mycophenolate mofetil in the 52-week study, but the total number of disease flares in the mycophenolate mofetil group was five times higher. Moreover, rituximab-treated patients received a markedly lower cumulative dose of prednisone as well.
“Rituximab has a superior overall benefit-risk profile, compared to mycophenolate mofetil, in patients with moderate to severe pemphigus vulgaris,” concluded Dr. Joly, professor of dermatology at the University of Rouen (France) and president of the French Society of Dermatology.
The study was undertaken because mycophenolate mofetil is commonly used as a corticosteroid-sparing drug in patients with pemphigus vulgaris, even though its efficacy for the treatment of this rare, severe autoimmune blistering disease is unproven, he explained.
In contrast, rituximab was approved by the Food and Drug Administration and European regulators for treatment of pemphigus vulgaris on the strength of the pivotal phase 3 Ritux 3 trial – also led by Dr. Joly – which demonstrated the superiority of this intravenously administered anti-CD20 monoclonal antibody plus short-term prednisone over high-dose corticosteroid monotherapy, which for decades had been the standard treatment despite its considerable toxicity burden (Lancet. 2017 May 20;389[10083]:2031-40).
An independently conducted analysis of Ritux 3 recently concluded that rituximab plus short-term prednisone was more effective than prednisone alone, with a lower risk of life-threatening, corticosteroid-related adverse events and less cumulative corticosteroid exposure (Br J Dermatol. 2019 Sep 5. doi: 10.1111/bjd.18482).
Also, an international panel of 93 pemphigus experts has declared that rituximab should be considered an evidence-based first-line therapy for moderate to-severe pemphigus (J Am Acad Dermatol. 2018 Feb 10. doi: 10.1016/j.jaad.2018.02.021).
The phase 3, placebo-controlled PEMPHIX trial randomized 135 patients with moderate or severe pemphigus at 49 academic medical centers in the United States and nine other countries to double-blind rituximab or mycophenolate mofetil on top of background oral prednisone at 1.0-1.5 mg/kg per day, with the steroid to be tapered and discontinued within 4-6 months.
The primary endpoint of the study was the proportion of patients in each study arm at week 52 who had achieved a sustained complete remission lasting for at least 16 weeks while off prednisone. The rate was 40.3% in the rituximab group and 9.5% with mycophenolate mofetil, for a 383% increased likelihood of sustained complete remission in the rituximab group.
In addition, all of the study’s secondary endpoints significantly favored rituximab. The median cumulative dose of corticosteroid was 2.7 g through 52 weeks in the rituximab arm, compared with 4 g with mycophenolate mofetil. The total number of disease flares over 52 weeks was 6 in the rituximab group and 44 in the mycophenolate arm. Five rituximab-treated patients experienced disease flares, as did 26 on mycophenolate. Thus, the likelihood of a flare was seven times lower with rituximab.
Scores on the Dermatology Life Quality Index improved by an average of 8.87 points from baseline to week 52 in the rituximab group versus 6 points with mycophenolate. And 62.7% of rituximab-treated patients had a week-52 Dermatology Life Quality Index score of 0, meaning no impact of the disease on their quality of life, compared with 25% of the mycophenolate group.
Dr. Joly characterized the safety profile of rituximab as “manageable, with acceptable tolerability.” About 9% of the rituximab group and 7.4% of mycophenolate-treated patients had one or more treatment-related adverse events, a nonsignificant difference. The rate of treatment-related serious infections was 3.0% with rituximab and 2.9% with mycophenolate. Serious infusion reactions leading to study withdrawal occurred in three patients on rituximab and one on mycophenolate. The rate of grade 3 or worse corticosteroid-related adverse events was 1.5% with rituximab and significantly greater at 7.4% with mycophenolate.
An additional 48-week safety assessment beyond the 52-week primary outcome is ongoing.
Asked what future role he sees for mycophenolate in pemphigus vulgaris, Dr. Joly replied that the only study in the literature that shows the drug outperforms placebo was seriously flawed. “In the future, it’s very likely that the indications for use of mycophenolate in pemphigus vulgaris will be fewer and fewer,” the dermatologist added.
In reply to a question about the merits of routine antibiotic prophylaxis against pneumocystis carinii pneumonia in patients taking rituximab for pemphigus vulgaris, Dr. Joly said the incidence isn’t sufficiently high to justify such practice. After all, he noted, there were no cases of pneumocystis carinii pneumonia in rituximab-treated patients in PEMPHIX and only one in Ritux 3.
EADV Scientific Programming Committee Chair Brigitte Dreno, MD, PhD, professor and head of dermatology at University Hospital in Nantes, France, inquired as to whether there’s a role for maintenance therapy in a potent rituximab-based treatment strategy such as utilized in PEMPHIX.
Definitely, Dr. Joly replied. However, further study is required to work out the best maintenance program.
“There are many arguments for maintenance therapy in these patients. For one, the frequency of relapses increases with the length of follow-up. Also, anti–desmoglein-specific T cells can still be detected after rituximab therapy, even in patients in complete remission. So there is a need for maintenance therapy, perhaps at months 6, 12, and 18, but the optimal regimen isn’t determined yet,” according to Dr. Joly.
PEMPHIX was sponsored by F. Hoffmann-La Roche. Dr. Joly reported serving as a consultant to Roche, Amgen, Principia Biopharma, and Argenx.
MADRID – Pascal Joly, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Not only did rituximab prove superior in terms of efficacy in the PEMPHIX trial, with a five times greater likelihood of achieving a complete remission lasting for at least 16 weeks while off oral corticosteroids than with mycophenolate mofetil in the 52-week study, but the total number of disease flares in the mycophenolate mofetil group was five times higher. Moreover, rituximab-treated patients received a markedly lower cumulative dose of prednisone as well.
“Rituximab has a superior overall benefit-risk profile, compared to mycophenolate mofetil, in patients with moderate to severe pemphigus vulgaris,” concluded Dr. Joly, professor of dermatology at the University of Rouen (France) and president of the French Society of Dermatology.
The study was undertaken because mycophenolate mofetil is commonly used as a corticosteroid-sparing drug in patients with pemphigus vulgaris, even though its efficacy for the treatment of this rare, severe autoimmune blistering disease is unproven, he explained.
In contrast, rituximab was approved by the Food and Drug Administration and European regulators for treatment of pemphigus vulgaris on the strength of the pivotal phase 3 Ritux 3 trial – also led by Dr. Joly – which demonstrated the superiority of this intravenously administered anti-CD20 monoclonal antibody plus short-term prednisone over high-dose corticosteroid monotherapy, which for decades had been the standard treatment despite its considerable toxicity burden (Lancet. 2017 May 20;389[10083]:2031-40).
An independently conducted analysis of Ritux 3 recently concluded that rituximab plus short-term prednisone was more effective than prednisone alone, with a lower risk of life-threatening, corticosteroid-related adverse events and less cumulative corticosteroid exposure (Br J Dermatol. 2019 Sep 5. doi: 10.1111/bjd.18482).
Also, an international panel of 93 pemphigus experts has declared that rituximab should be considered an evidence-based first-line therapy for moderate to-severe pemphigus (J Am Acad Dermatol. 2018 Feb 10. doi: 10.1016/j.jaad.2018.02.021).
The phase 3, placebo-controlled PEMPHIX trial randomized 135 patients with moderate or severe pemphigus at 49 academic medical centers in the United States and nine other countries to double-blind rituximab or mycophenolate mofetil on top of background oral prednisone at 1.0-1.5 mg/kg per day, with the steroid to be tapered and discontinued within 4-6 months.
The primary endpoint of the study was the proportion of patients in each study arm at week 52 who had achieved a sustained complete remission lasting for at least 16 weeks while off prednisone. The rate was 40.3% in the rituximab group and 9.5% with mycophenolate mofetil, for a 383% increased likelihood of sustained complete remission in the rituximab group.
In addition, all of the study’s secondary endpoints significantly favored rituximab. The median cumulative dose of corticosteroid was 2.7 g through 52 weeks in the rituximab arm, compared with 4 g with mycophenolate mofetil. The total number of disease flares over 52 weeks was 6 in the rituximab group and 44 in the mycophenolate arm. Five rituximab-treated patients experienced disease flares, as did 26 on mycophenolate. Thus, the likelihood of a flare was seven times lower with rituximab.
Scores on the Dermatology Life Quality Index improved by an average of 8.87 points from baseline to week 52 in the rituximab group versus 6 points with mycophenolate. And 62.7% of rituximab-treated patients had a week-52 Dermatology Life Quality Index score of 0, meaning no impact of the disease on their quality of life, compared with 25% of the mycophenolate group.
Dr. Joly characterized the safety profile of rituximab as “manageable, with acceptable tolerability.” About 9% of the rituximab group and 7.4% of mycophenolate-treated patients had one or more treatment-related adverse events, a nonsignificant difference. The rate of treatment-related serious infections was 3.0% with rituximab and 2.9% with mycophenolate. Serious infusion reactions leading to study withdrawal occurred in three patients on rituximab and one on mycophenolate. The rate of grade 3 or worse corticosteroid-related adverse events was 1.5% with rituximab and significantly greater at 7.4% with mycophenolate.
An additional 48-week safety assessment beyond the 52-week primary outcome is ongoing.
Asked what future role he sees for mycophenolate in pemphigus vulgaris, Dr. Joly replied that the only study in the literature that shows the drug outperforms placebo was seriously flawed. “In the future, it’s very likely that the indications for use of mycophenolate in pemphigus vulgaris will be fewer and fewer,” the dermatologist added.
In reply to a question about the merits of routine antibiotic prophylaxis against pneumocystis carinii pneumonia in patients taking rituximab for pemphigus vulgaris, Dr. Joly said the incidence isn’t sufficiently high to justify such practice. After all, he noted, there were no cases of pneumocystis carinii pneumonia in rituximab-treated patients in PEMPHIX and only one in Ritux 3.
EADV Scientific Programming Committee Chair Brigitte Dreno, MD, PhD, professor and head of dermatology at University Hospital in Nantes, France, inquired as to whether there’s a role for maintenance therapy in a potent rituximab-based treatment strategy such as utilized in PEMPHIX.
Definitely, Dr. Joly replied. However, further study is required to work out the best maintenance program.
“There are many arguments for maintenance therapy in these patients. For one, the frequency of relapses increases with the length of follow-up. Also, anti–desmoglein-specific T cells can still be detected after rituximab therapy, even in patients in complete remission. So there is a need for maintenance therapy, perhaps at months 6, 12, and 18, but the optimal regimen isn’t determined yet,” according to Dr. Joly.
PEMPHIX was sponsored by F. Hoffmann-La Roche. Dr. Joly reported serving as a consultant to Roche, Amgen, Principia Biopharma, and Argenx.
MADRID – Pascal Joly, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.
Not only did rituximab prove superior in terms of efficacy in the PEMPHIX trial, with a five times greater likelihood of achieving a complete remission lasting for at least 16 weeks while off oral corticosteroids than with mycophenolate mofetil in the 52-week study, but the total number of disease flares in the mycophenolate mofetil group was five times higher. Moreover, rituximab-treated patients received a markedly lower cumulative dose of prednisone as well.
“Rituximab has a superior overall benefit-risk profile, compared to mycophenolate mofetil, in patients with moderate to severe pemphigus vulgaris,” concluded Dr. Joly, professor of dermatology at the University of Rouen (France) and president of the French Society of Dermatology.
The study was undertaken because mycophenolate mofetil is commonly used as a corticosteroid-sparing drug in patients with pemphigus vulgaris, even though its efficacy for the treatment of this rare, severe autoimmune blistering disease is unproven, he explained.
In contrast, rituximab was approved by the Food and Drug Administration and European regulators for treatment of pemphigus vulgaris on the strength of the pivotal phase 3 Ritux 3 trial – also led by Dr. Joly – which demonstrated the superiority of this intravenously administered anti-CD20 monoclonal antibody plus short-term prednisone over high-dose corticosteroid monotherapy, which for decades had been the standard treatment despite its considerable toxicity burden (Lancet. 2017 May 20;389[10083]:2031-40).
An independently conducted analysis of Ritux 3 recently concluded that rituximab plus short-term prednisone was more effective than prednisone alone, with a lower risk of life-threatening, corticosteroid-related adverse events and less cumulative corticosteroid exposure (Br J Dermatol. 2019 Sep 5. doi: 10.1111/bjd.18482).
Also, an international panel of 93 pemphigus experts has declared that rituximab should be considered an evidence-based first-line therapy for moderate to-severe pemphigus (J Am Acad Dermatol. 2018 Feb 10. doi: 10.1016/j.jaad.2018.02.021).
The phase 3, placebo-controlled PEMPHIX trial randomized 135 patients with moderate or severe pemphigus at 49 academic medical centers in the United States and nine other countries to double-blind rituximab or mycophenolate mofetil on top of background oral prednisone at 1.0-1.5 mg/kg per day, with the steroid to be tapered and discontinued within 4-6 months.
The primary endpoint of the study was the proportion of patients in each study arm at week 52 who had achieved a sustained complete remission lasting for at least 16 weeks while off prednisone. The rate was 40.3% in the rituximab group and 9.5% with mycophenolate mofetil, for a 383% increased likelihood of sustained complete remission in the rituximab group.
In addition, all of the study’s secondary endpoints significantly favored rituximab. The median cumulative dose of corticosteroid was 2.7 g through 52 weeks in the rituximab arm, compared with 4 g with mycophenolate mofetil. The total number of disease flares over 52 weeks was 6 in the rituximab group and 44 in the mycophenolate arm. Five rituximab-treated patients experienced disease flares, as did 26 on mycophenolate. Thus, the likelihood of a flare was seven times lower with rituximab.
Scores on the Dermatology Life Quality Index improved by an average of 8.87 points from baseline to week 52 in the rituximab group versus 6 points with mycophenolate. And 62.7% of rituximab-treated patients had a week-52 Dermatology Life Quality Index score of 0, meaning no impact of the disease on their quality of life, compared with 25% of the mycophenolate group.
Dr. Joly characterized the safety profile of rituximab as “manageable, with acceptable tolerability.” About 9% of the rituximab group and 7.4% of mycophenolate-treated patients had one or more treatment-related adverse events, a nonsignificant difference. The rate of treatment-related serious infections was 3.0% with rituximab and 2.9% with mycophenolate. Serious infusion reactions leading to study withdrawal occurred in three patients on rituximab and one on mycophenolate. The rate of grade 3 or worse corticosteroid-related adverse events was 1.5% with rituximab and significantly greater at 7.4% with mycophenolate.
An additional 48-week safety assessment beyond the 52-week primary outcome is ongoing.
Asked what future role he sees for mycophenolate in pemphigus vulgaris, Dr. Joly replied that the only study in the literature that shows the drug outperforms placebo was seriously flawed. “In the future, it’s very likely that the indications for use of mycophenolate in pemphigus vulgaris will be fewer and fewer,” the dermatologist added.
In reply to a question about the merits of routine antibiotic prophylaxis against pneumocystis carinii pneumonia in patients taking rituximab for pemphigus vulgaris, Dr. Joly said the incidence isn’t sufficiently high to justify such practice. After all, he noted, there were no cases of pneumocystis carinii pneumonia in rituximab-treated patients in PEMPHIX and only one in Ritux 3.
EADV Scientific Programming Committee Chair Brigitte Dreno, MD, PhD, professor and head of dermatology at University Hospital in Nantes, France, inquired as to whether there’s a role for maintenance therapy in a potent rituximab-based treatment strategy such as utilized in PEMPHIX.
Definitely, Dr. Joly replied. However, further study is required to work out the best maintenance program.
“There are many arguments for maintenance therapy in these patients. For one, the frequency of relapses increases with the length of follow-up. Also, anti–desmoglein-specific T cells can still be detected after rituximab therapy, even in patients in complete remission. So there is a need for maintenance therapy, perhaps at months 6, 12, and 18, but the optimal regimen isn’t determined yet,” according to Dr. Joly.
PEMPHIX was sponsored by F. Hoffmann-La Roche. Dr. Joly reported serving as a consultant to Roche, Amgen, Principia Biopharma, and Argenx.
REPORTING FROM THE EADV CONGRESS
Hyperhidrosis treatment options update
SEATTLE – , David Pariser, MD, said at the annual Coastal Dermatology Symposium.
Hyperhidrosis is among the dermatological conditions that have the greatest impact on quality of life, and it can be particularly concerning to teens, said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. He referred to some new developments for an old, often misunderstood, standby: antiperspirants. “I am amazed that many people do not know the difference between an antiperspirant and a deodorant,” he said, pointing out that antiperspirants contain active ingredients – aluminum and zirconium salts – that block sweat glands, while deodorants contain a masking fragrance.
There are new-generation topical antiperspirants available over the counter, with descriptions that include “clinical strength” or “clinical protection” on the labels; they come in a box and cost about twice as much as standard products. “But they are better, and they work just as well as some of the commercial preparations,” Dr. Pariser said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.
One issue he highlighted was that antiperspirants are often misapplied. They shouldn’t be applied on wet skin because they react with water to create hydrochloric acid, which can irritate the skin, he said. The best time to apply an antiperspirant is right before bedtime, since it gives the salts time to clog sweat pores before sweat or water can interfere. “The plugs last for a couple of days,” so there’s no need to worry about rinsing the product off during a morning shower, he noted.
Additional therapeutic options include agents like oral glycopyrrolate, starting at a low dose (1 mg twice per day), increasing by 1 mg/day weekly until efficacy is achieved or limited by adverse events. There is also a glycopyrrolate oral solution 1mg/5ml (Cuvposa) that can be used in children.
A topical version of the anticholinergic glycopyrronium tosylate, applied using an infused cloth, was approved for treating axillary hyperhidrosis in June2018 and offers the potential for an enhanced local anticholinergic effect. Dr. Pariser, one of the authors, discussed the recently published results of two pivotal studies that found good improvement in a specially-designed quality of life endpoint (J Am Acad Derm. 2019; Jan;80[1]:128-138.e2).
Efficacy in a subanalysis of 44 pediatric subjects (ages 9-16 years) was similar as those reported in adults, and the rate of those reporting dry mouth (24% in both age groups) was similar. Of concern was a 16% rate of mydriasis in the pediatric group, compared with 6% in the older group. One patient even wound up in the emergency room for a stroke work-up as a result, said Dr. Pariser, who is confident that the problem was caused by inadvertent exposure to the eye during application. He advises patients to avoid contact with the eyes.
Other approaches to treatment of hyperhidrosis include oxybutynin, iontophoresis, an microwave thermolysis (which may also reduce odor and hair). Endoscopic thoracic sympathectomy is effective but is the most invasive option; botulinum toxin is a minimally invasive alternative to surgery.
For those who sweat when they experience anxiety, propranolol 5-10 mg taken about 1 hour before an event that could cause hyperhydrosis can be effective, said Dr. Pariser, who recommends a test dose. “I don’t normally tell patients to try something at home. But they should try this at home” before using it prior to an important event, he added.
Dr. Pariser is a consultant and/or investigator for Dermira, Brickell Biotech, TheraVida, Atacama, TDI Surgitech, Dermavant, and Revance Therapeutics. He has not done commercial speaking, has not been on speaker’s bureaus, and has no stock or options in any company.
This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – , David Pariser, MD, said at the annual Coastal Dermatology Symposium.
Hyperhidrosis is among the dermatological conditions that have the greatest impact on quality of life, and it can be particularly concerning to teens, said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. He referred to some new developments for an old, often misunderstood, standby: antiperspirants. “I am amazed that many people do not know the difference between an antiperspirant and a deodorant,” he said, pointing out that antiperspirants contain active ingredients – aluminum and zirconium salts – that block sweat glands, while deodorants contain a masking fragrance.
There are new-generation topical antiperspirants available over the counter, with descriptions that include “clinical strength” or “clinical protection” on the labels; they come in a box and cost about twice as much as standard products. “But they are better, and they work just as well as some of the commercial preparations,” Dr. Pariser said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.
One issue he highlighted was that antiperspirants are often misapplied. They shouldn’t be applied on wet skin because they react with water to create hydrochloric acid, which can irritate the skin, he said. The best time to apply an antiperspirant is right before bedtime, since it gives the salts time to clog sweat pores before sweat or water can interfere. “The plugs last for a couple of days,” so there’s no need to worry about rinsing the product off during a morning shower, he noted.
Additional therapeutic options include agents like oral glycopyrrolate, starting at a low dose (1 mg twice per day), increasing by 1 mg/day weekly until efficacy is achieved or limited by adverse events. There is also a glycopyrrolate oral solution 1mg/5ml (Cuvposa) that can be used in children.
A topical version of the anticholinergic glycopyrronium tosylate, applied using an infused cloth, was approved for treating axillary hyperhidrosis in June2018 and offers the potential for an enhanced local anticholinergic effect. Dr. Pariser, one of the authors, discussed the recently published results of two pivotal studies that found good improvement in a specially-designed quality of life endpoint (J Am Acad Derm. 2019; Jan;80[1]:128-138.e2).
Efficacy in a subanalysis of 44 pediatric subjects (ages 9-16 years) was similar as those reported in adults, and the rate of those reporting dry mouth (24% in both age groups) was similar. Of concern was a 16% rate of mydriasis in the pediatric group, compared with 6% in the older group. One patient even wound up in the emergency room for a stroke work-up as a result, said Dr. Pariser, who is confident that the problem was caused by inadvertent exposure to the eye during application. He advises patients to avoid contact with the eyes.
Other approaches to treatment of hyperhidrosis include oxybutynin, iontophoresis, an microwave thermolysis (which may also reduce odor and hair). Endoscopic thoracic sympathectomy is effective but is the most invasive option; botulinum toxin is a minimally invasive alternative to surgery.
For those who sweat when they experience anxiety, propranolol 5-10 mg taken about 1 hour before an event that could cause hyperhydrosis can be effective, said Dr. Pariser, who recommends a test dose. “I don’t normally tell patients to try something at home. But they should try this at home” before using it prior to an important event, he added.
Dr. Pariser is a consultant and/or investigator for Dermira, Brickell Biotech, TheraVida, Atacama, TDI Surgitech, Dermavant, and Revance Therapeutics. He has not done commercial speaking, has not been on speaker’s bureaus, and has no stock or options in any company.
This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – , David Pariser, MD, said at the annual Coastal Dermatology Symposium.
Hyperhidrosis is among the dermatological conditions that have the greatest impact on quality of life, and it can be particularly concerning to teens, said Dr. Pariser, professor of dermatology at Eastern Virginia Medical School, Norfolk. He referred to some new developments for an old, often misunderstood, standby: antiperspirants. “I am amazed that many people do not know the difference between an antiperspirant and a deodorant,” he said, pointing out that antiperspirants contain active ingredients – aluminum and zirconium salts – that block sweat glands, while deodorants contain a masking fragrance.
There are new-generation topical antiperspirants available over the counter, with descriptions that include “clinical strength” or “clinical protection” on the labels; they come in a box and cost about twice as much as standard products. “But they are better, and they work just as well as some of the commercial preparations,” Dr. Pariser said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education.
One issue he highlighted was that antiperspirants are often misapplied. They shouldn’t be applied on wet skin because they react with water to create hydrochloric acid, which can irritate the skin, he said. The best time to apply an antiperspirant is right before bedtime, since it gives the salts time to clog sweat pores before sweat or water can interfere. “The plugs last for a couple of days,” so there’s no need to worry about rinsing the product off during a morning shower, he noted.
Additional therapeutic options include agents like oral glycopyrrolate, starting at a low dose (1 mg twice per day), increasing by 1 mg/day weekly until efficacy is achieved or limited by adverse events. There is also a glycopyrrolate oral solution 1mg/5ml (Cuvposa) that can be used in children.
A topical version of the anticholinergic glycopyrronium tosylate, applied using an infused cloth, was approved for treating axillary hyperhidrosis in June2018 and offers the potential for an enhanced local anticholinergic effect. Dr. Pariser, one of the authors, discussed the recently published results of two pivotal studies that found good improvement in a specially-designed quality of life endpoint (J Am Acad Derm. 2019; Jan;80[1]:128-138.e2).
Efficacy in a subanalysis of 44 pediatric subjects (ages 9-16 years) was similar as those reported in adults, and the rate of those reporting dry mouth (24% in both age groups) was similar. Of concern was a 16% rate of mydriasis in the pediatric group, compared with 6% in the older group. One patient even wound up in the emergency room for a stroke work-up as a result, said Dr. Pariser, who is confident that the problem was caused by inadvertent exposure to the eye during application. He advises patients to avoid contact with the eyes.
Other approaches to treatment of hyperhidrosis include oxybutynin, iontophoresis, an microwave thermolysis (which may also reduce odor and hair). Endoscopic thoracic sympathectomy is effective but is the most invasive option; botulinum toxin is a minimally invasive alternative to surgery.
For those who sweat when they experience anxiety, propranolol 5-10 mg taken about 1 hour before an event that could cause hyperhydrosis can be effective, said Dr. Pariser, who recommends a test dose. “I don’t normally tell patients to try something at home. But they should try this at home” before using it prior to an important event, he added.
Dr. Pariser is a consultant and/or investigator for Dermira, Brickell Biotech, TheraVida, Atacama, TDI Surgitech, Dermavant, and Revance Therapeutics. He has not done commercial speaking, has not been on speaker’s bureaus, and has no stock or options in any company.
This publication and Global Academy for Medical Education are owned by the same parent company.
EXPERT ANALYSIS FROM COASTAL DERM
FDA approves afamelanotide for treatment of rare condition with light-induced pain
The Food and Drug Administration has approved , a rare condition that causes extremely painful reactions when skin is exposed to light, according to an FDA announcement.
This is the first treatment approved to help patients with this condition increase their exposure to light, according to the release.
Afamelanotide, administered in a subcutaneous implant, is a melanocortin-1 receptor (MC1-R) agonist, which “increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources,” the release says.
Approval is based on a pair of parallel-group clinical trials that compared the number of hours spent in sunlight in the treatment and placebo groups. The first trial enrolled 93 patients; 48 received afamelanotide. The treated patients spent a median of 61 hours in total over 180 days in direct sunlight between 10 a.m. and 6 p.m. on days with no pain, compared with 41 hours for patients taking placebo.
The second trial assessed the total number of hours over 270 days spent outdoors between 10 a.m. and 3 p.m. on days with no pain for which “most of the day” was spent in direct sunlight. In this study, 38 patients treated with afamelanotide spent a median total of 6 hours, compared with 0.75 hours among the remaining 36 who were taking a placebo.
The most common side effects include implant site reaction, nausea, and oropharyngeal pain. The implant should be administered only by trained professionals. Because afamelanotide may cause skin darkening, it’s recommended that patients should undergo twice-yearly skin examinations. Patients are also encouraged to maintain sun protection measures to help prevent phototoxic reactions.
“Today’s approval is one example of the FDA’s ongoing commitment to encourage industry innovation of therapies to treat rare diseases, and work with drug developers to make promising new therapies available to patients as safely and efficiently as possible,” said Julie Beitz, MD, director of FDA’s Center for Drug Evaluation and Research Office of Drug Evaluation III in the FDA release.
The Food and Drug Administration has approved , a rare condition that causes extremely painful reactions when skin is exposed to light, according to an FDA announcement.
This is the first treatment approved to help patients with this condition increase their exposure to light, according to the release.
Afamelanotide, administered in a subcutaneous implant, is a melanocortin-1 receptor (MC1-R) agonist, which “increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources,” the release says.
Approval is based on a pair of parallel-group clinical trials that compared the number of hours spent in sunlight in the treatment and placebo groups. The first trial enrolled 93 patients; 48 received afamelanotide. The treated patients spent a median of 61 hours in total over 180 days in direct sunlight between 10 a.m. and 6 p.m. on days with no pain, compared with 41 hours for patients taking placebo.
The second trial assessed the total number of hours over 270 days spent outdoors between 10 a.m. and 3 p.m. on days with no pain for which “most of the day” was spent in direct sunlight. In this study, 38 patients treated with afamelanotide spent a median total of 6 hours, compared with 0.75 hours among the remaining 36 who were taking a placebo.
The most common side effects include implant site reaction, nausea, and oropharyngeal pain. The implant should be administered only by trained professionals. Because afamelanotide may cause skin darkening, it’s recommended that patients should undergo twice-yearly skin examinations. Patients are also encouraged to maintain sun protection measures to help prevent phototoxic reactions.
“Today’s approval is one example of the FDA’s ongoing commitment to encourage industry innovation of therapies to treat rare diseases, and work with drug developers to make promising new therapies available to patients as safely and efficiently as possible,” said Julie Beitz, MD, director of FDA’s Center for Drug Evaluation and Research Office of Drug Evaluation III in the FDA release.
The Food and Drug Administration has approved , a rare condition that causes extremely painful reactions when skin is exposed to light, according to an FDA announcement.
This is the first treatment approved to help patients with this condition increase their exposure to light, according to the release.
Afamelanotide, administered in a subcutaneous implant, is a melanocortin-1 receptor (MC1-R) agonist, which “increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources,” the release says.
Approval is based on a pair of parallel-group clinical trials that compared the number of hours spent in sunlight in the treatment and placebo groups. The first trial enrolled 93 patients; 48 received afamelanotide. The treated patients spent a median of 61 hours in total over 180 days in direct sunlight between 10 a.m. and 6 p.m. on days with no pain, compared with 41 hours for patients taking placebo.
The second trial assessed the total number of hours over 270 days spent outdoors between 10 a.m. and 3 p.m. on days with no pain for which “most of the day” was spent in direct sunlight. In this study, 38 patients treated with afamelanotide spent a median total of 6 hours, compared with 0.75 hours among the remaining 36 who were taking a placebo.
The most common side effects include implant site reaction, nausea, and oropharyngeal pain. The implant should be administered only by trained professionals. Because afamelanotide may cause skin darkening, it’s recommended that patients should undergo twice-yearly skin examinations. Patients are also encouraged to maintain sun protection measures to help prevent phototoxic reactions.
“Today’s approval is one example of the FDA’s ongoing commitment to encourage industry innovation of therapies to treat rare diseases, and work with drug developers to make promising new therapies available to patients as safely and efficiently as possible,” said Julie Beitz, MD, director of FDA’s Center for Drug Evaluation and Research Office of Drug Evaluation III in the FDA release.
Photodermatoses: Differential diagnosis includes sunscreen allergy, connective tissue disease
SEATTLE – according to Vincent DeLeo, MD, of the department of dermatology at the University of Southern California, Los Angeles, who discussed common diagnoses at the annual Coastal Dermatology Symposium.
“They’re not common bread-and-butter dermatitis, like acne rosacea. Many people feel uncomfortable trying to work out the differential diagnosis when they see someone who comes in with what either the patient or the physician thinks is a reaction to the sun,” Dr. DeLeo said in an interview at the meeting.
“Usually, the best clue is the distribution of the rash or lesion,” which often are on the backs of the hands or on the arms from the sleeves down, he added. “When you see that, you should think of a photosensitive eruption,” and consider a differential diagnosis, using “certain tests, asking questions, and looking at the morphology and distribution of the reaction.”
The most common of the photodermatoses is polymorphous light eruption, which typically occurs in people on vacation, often among those who live in temperate climates and react violently to sun overexposure. “You usually have to rule out things like connective tissue disease by getting serology,” Dr. DeLeo noted in the interview.
In general, these patients either present with a reaction or describe a rash that has since cleared up. When a patient is describing a problem that has disappeared, he or she may have a photo of the reaction on their phone, which can be helpful, he said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.
Some photodermatoses are characterized by tell-tale rashes indicative of a connective tissue disease like lupus or dermatomyositis, which can be followed up with biopsy and serology to confirm a diagnosis, said Dr. DeLeo, who is also professor emeritus of dermatology at the Icahn School of Medicine at Mount Sinai, New York. Other patterns, such as blisters on the hands, should prompt tests for porphyria cutanea tarda, which requires a 24-hour urine test to confirm.
But reactions in sun-exposed areas can also be caused by drug-induced photosensitivity and drugs such as NSAIDs, antibiotics, and diuretics, among others, Dr. DeLeo said.
Another common reaction can occur with exposure to photosensitizing plant materials, resulting in blisters combined with altered pigmentation. Most frequently, these reactions are caused by exposure to limes, which contain psoralens that absorb light and produce the reaction. “That is a clinical diagnosis and we can recognize that because, like poison ivy, it is usually a streaky kind of reaction in a distinct pattern. You don’t need [additional] tests for that,” he said. This can occur, for example, after making cocktails, he said, describing an example of parents who had been mixing drinks and then picked up their child. Later, they brought the child to the ED with a hand-shaped rash, and treating physicians contacted social services out of fears of child abuse.
In some cases, patients who present with no rash can elicit the problem. Solar urticaria can produce hives on demand – ask a patient to go out in the sun and return after a few minutes, and a rash will generally appear, Dr. DeLeo advised.
Patients might want to take steps to avoid such problems and there are several options available to do so, Dr. DeLeo noted. There is some evidence of efficacy for photoprotection for an extract from a fern plant found in Central and South America, a product called Heliocare, in a study sponsored by the manufacturer, Ferndale Healthcare (J Clin Aesthet Dermatol. 2015 Feb;8[2]:19-23). Patients can also undergo two or three treatments of phototherapy for 3-4 weeks in advance of a trip in order to “harden” the skin and reduce the chances of an overreaction.
Dr. DeLeo presented a simplified guide to use when considering differential diagnoses in patients with photodermatoses.
- Solar urticaria occurs quickly upon exposure and is short lived.
- Polymorphous light eruption usually occurs during a vacation and does not affect the face.
- A sun-related eczematous rash affecting the face, which recurs, is typically photoallergy to sunscreen.
- A chronic, severe dermatitis seen in a photodistribution pattern could be chronic actinic dermatitis. The patient should undergo phototesting. A biopsy of a severe case may resemble lymphoma.
- In photosensitive individuals with an uncertain diagnosis, serology testing for connective tissue disease should be performed to rule out lupus or dermatomyositis.
- When the patient has a rash in only sun-exposed areas, as well as a history of exposure to photosensitizing drugs, the drug should be discontinued to see if the rash disappears.
- Porphyria cutanea tarda is diagnosed with a 24-hour urine test that reveals at least five times normal uroporphyrin levels, along with hemochromatosis polymorphisms. Levels of uroporphyrin that are elevated but not five times normal are suggestive of pseudoporphyria.
- Phototoxic contact dermatitis caused by plants often results in unusual distributions.
- Hispanic individuals with a photodistributed rash, especially in the presence of cheilitis, may have actinic prurigo.
Dr. DeLeo is a consultant for Estee Lauder. The annual Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – according to Vincent DeLeo, MD, of the department of dermatology at the University of Southern California, Los Angeles, who discussed common diagnoses at the annual Coastal Dermatology Symposium.
“They’re not common bread-and-butter dermatitis, like acne rosacea. Many people feel uncomfortable trying to work out the differential diagnosis when they see someone who comes in with what either the patient or the physician thinks is a reaction to the sun,” Dr. DeLeo said in an interview at the meeting.
“Usually, the best clue is the distribution of the rash or lesion,” which often are on the backs of the hands or on the arms from the sleeves down, he added. “When you see that, you should think of a photosensitive eruption,” and consider a differential diagnosis, using “certain tests, asking questions, and looking at the morphology and distribution of the reaction.”
The most common of the photodermatoses is polymorphous light eruption, which typically occurs in people on vacation, often among those who live in temperate climates and react violently to sun overexposure. “You usually have to rule out things like connective tissue disease by getting serology,” Dr. DeLeo noted in the interview.
In general, these patients either present with a reaction or describe a rash that has since cleared up. When a patient is describing a problem that has disappeared, he or she may have a photo of the reaction on their phone, which can be helpful, he said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.
Some photodermatoses are characterized by tell-tale rashes indicative of a connective tissue disease like lupus or dermatomyositis, which can be followed up with biopsy and serology to confirm a diagnosis, said Dr. DeLeo, who is also professor emeritus of dermatology at the Icahn School of Medicine at Mount Sinai, New York. Other patterns, such as blisters on the hands, should prompt tests for porphyria cutanea tarda, which requires a 24-hour urine test to confirm.
But reactions in sun-exposed areas can also be caused by drug-induced photosensitivity and drugs such as NSAIDs, antibiotics, and diuretics, among others, Dr. DeLeo said.
Another common reaction can occur with exposure to photosensitizing plant materials, resulting in blisters combined with altered pigmentation. Most frequently, these reactions are caused by exposure to limes, which contain psoralens that absorb light and produce the reaction. “That is a clinical diagnosis and we can recognize that because, like poison ivy, it is usually a streaky kind of reaction in a distinct pattern. You don’t need [additional] tests for that,” he said. This can occur, for example, after making cocktails, he said, describing an example of parents who had been mixing drinks and then picked up their child. Later, they brought the child to the ED with a hand-shaped rash, and treating physicians contacted social services out of fears of child abuse.
In some cases, patients who present with no rash can elicit the problem. Solar urticaria can produce hives on demand – ask a patient to go out in the sun and return after a few minutes, and a rash will generally appear, Dr. DeLeo advised.
Patients might want to take steps to avoid such problems and there are several options available to do so, Dr. DeLeo noted. There is some evidence of efficacy for photoprotection for an extract from a fern plant found in Central and South America, a product called Heliocare, in a study sponsored by the manufacturer, Ferndale Healthcare (J Clin Aesthet Dermatol. 2015 Feb;8[2]:19-23). Patients can also undergo two or three treatments of phototherapy for 3-4 weeks in advance of a trip in order to “harden” the skin and reduce the chances of an overreaction.
Dr. DeLeo presented a simplified guide to use when considering differential diagnoses in patients with photodermatoses.
- Solar urticaria occurs quickly upon exposure and is short lived.
- Polymorphous light eruption usually occurs during a vacation and does not affect the face.
- A sun-related eczematous rash affecting the face, which recurs, is typically photoallergy to sunscreen.
- A chronic, severe dermatitis seen in a photodistribution pattern could be chronic actinic dermatitis. The patient should undergo phototesting. A biopsy of a severe case may resemble lymphoma.
- In photosensitive individuals with an uncertain diagnosis, serology testing for connective tissue disease should be performed to rule out lupus or dermatomyositis.
- When the patient has a rash in only sun-exposed areas, as well as a history of exposure to photosensitizing drugs, the drug should be discontinued to see if the rash disappears.
- Porphyria cutanea tarda is diagnosed with a 24-hour urine test that reveals at least five times normal uroporphyrin levels, along with hemochromatosis polymorphisms. Levels of uroporphyrin that are elevated but not five times normal are suggestive of pseudoporphyria.
- Phototoxic contact dermatitis caused by plants often results in unusual distributions.
- Hispanic individuals with a photodistributed rash, especially in the presence of cheilitis, may have actinic prurigo.
Dr. DeLeo is a consultant for Estee Lauder. The annual Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – according to Vincent DeLeo, MD, of the department of dermatology at the University of Southern California, Los Angeles, who discussed common diagnoses at the annual Coastal Dermatology Symposium.
“They’re not common bread-and-butter dermatitis, like acne rosacea. Many people feel uncomfortable trying to work out the differential diagnosis when they see someone who comes in with what either the patient or the physician thinks is a reaction to the sun,” Dr. DeLeo said in an interview at the meeting.
“Usually, the best clue is the distribution of the rash or lesion,” which often are on the backs of the hands or on the arms from the sleeves down, he added. “When you see that, you should think of a photosensitive eruption,” and consider a differential diagnosis, using “certain tests, asking questions, and looking at the morphology and distribution of the reaction.”
The most common of the photodermatoses is polymorphous light eruption, which typically occurs in people on vacation, often among those who live in temperate climates and react violently to sun overexposure. “You usually have to rule out things like connective tissue disease by getting serology,” Dr. DeLeo noted in the interview.
In general, these patients either present with a reaction or describe a rash that has since cleared up. When a patient is describing a problem that has disappeared, he or she may have a photo of the reaction on their phone, which can be helpful, he said at the meeting jointly presented by the University of Louisville and Global Academy for Medical Education.
Some photodermatoses are characterized by tell-tale rashes indicative of a connective tissue disease like lupus or dermatomyositis, which can be followed up with biopsy and serology to confirm a diagnosis, said Dr. DeLeo, who is also professor emeritus of dermatology at the Icahn School of Medicine at Mount Sinai, New York. Other patterns, such as blisters on the hands, should prompt tests for porphyria cutanea tarda, which requires a 24-hour urine test to confirm.
But reactions in sun-exposed areas can also be caused by drug-induced photosensitivity and drugs such as NSAIDs, antibiotics, and diuretics, among others, Dr. DeLeo said.
Another common reaction can occur with exposure to photosensitizing plant materials, resulting in blisters combined with altered pigmentation. Most frequently, these reactions are caused by exposure to limes, which contain psoralens that absorb light and produce the reaction. “That is a clinical diagnosis and we can recognize that because, like poison ivy, it is usually a streaky kind of reaction in a distinct pattern. You don’t need [additional] tests for that,” he said. This can occur, for example, after making cocktails, he said, describing an example of parents who had been mixing drinks and then picked up their child. Later, they brought the child to the ED with a hand-shaped rash, and treating physicians contacted social services out of fears of child abuse.
In some cases, patients who present with no rash can elicit the problem. Solar urticaria can produce hives on demand – ask a patient to go out in the sun and return after a few minutes, and a rash will generally appear, Dr. DeLeo advised.
Patients might want to take steps to avoid such problems and there are several options available to do so, Dr. DeLeo noted. There is some evidence of efficacy for photoprotection for an extract from a fern plant found in Central and South America, a product called Heliocare, in a study sponsored by the manufacturer, Ferndale Healthcare (J Clin Aesthet Dermatol. 2015 Feb;8[2]:19-23). Patients can also undergo two or three treatments of phototherapy for 3-4 weeks in advance of a trip in order to “harden” the skin and reduce the chances of an overreaction.
Dr. DeLeo presented a simplified guide to use when considering differential diagnoses in patients with photodermatoses.
- Solar urticaria occurs quickly upon exposure and is short lived.
- Polymorphous light eruption usually occurs during a vacation and does not affect the face.
- A sun-related eczematous rash affecting the face, which recurs, is typically photoallergy to sunscreen.
- A chronic, severe dermatitis seen in a photodistribution pattern could be chronic actinic dermatitis. The patient should undergo phototesting. A biopsy of a severe case may resemble lymphoma.
- In photosensitive individuals with an uncertain diagnosis, serology testing for connective tissue disease should be performed to rule out lupus or dermatomyositis.
- When the patient has a rash in only sun-exposed areas, as well as a history of exposure to photosensitizing drugs, the drug should be discontinued to see if the rash disappears.
- Porphyria cutanea tarda is diagnosed with a 24-hour urine test that reveals at least five times normal uroporphyrin levels, along with hemochromatosis polymorphisms. Levels of uroporphyrin that are elevated but not five times normal are suggestive of pseudoporphyria.
- Phototoxic contact dermatitis caused by plants often results in unusual distributions.
- Hispanic individuals with a photodistributed rash, especially in the presence of cheilitis, may have actinic prurigo.
Dr. DeLeo is a consultant for Estee Lauder. The annual Coastal Dermatology Symposium is jointly presented by the University of Louisville and Global Academy for Medical Education. This publication and Global Academy for Medical Education are owned by the same parent company.
EXPERT ANALYSIS FROM COASTAL DERM
Twitter Chat: Skin Cancer
Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma.
Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.
What will the conversation cover?
Q1: What are the most common types of skin cancer?
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?
Follow us here: @MDedgeDerm | @MDedgeTweets | #MDedgeChats
About Dr. Rossi:
Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York. He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.
His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.
Research and Publications by Dr. Rossi
About Dr. Heath:
Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers.
Research and publications by Dr. Heath
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo.
About Dr. Croley:
Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach.
Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.
Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”
Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article.
Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality.
In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.
- “Doctor, Do I Need a Skin Check?”
- Assessing the effectiveness of knowledge-based interventions in skin of color populations.
- Melanoma in US Hispanics
- Podcast: Sunscreen update from Dr. Vincent DeLeo
- Windshield and UV exposure
- Racial, ethnic minorities often don’t practice sun-protective behaviors.
- Sunscreen regulations and advice for your patients.
Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma.
Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.
What will the conversation cover?
Q1: What are the most common types of skin cancer?
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?
Follow us here: @MDedgeDerm | @MDedgeTweets | #MDedgeChats
About Dr. Rossi:
Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York. He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.
His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.
Research and Publications by Dr. Rossi
About Dr. Heath:
Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers.
Research and publications by Dr. Heath
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo.
About Dr. Croley:
Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach.
Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.
Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”
Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article.
Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality.
In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.
- “Doctor, Do I Need a Skin Check?”
- Assessing the effectiveness of knowledge-based interventions in skin of color populations.
- Melanoma in US Hispanics
- Podcast: Sunscreen update from Dr. Vincent DeLeo
- Windshield and UV exposure
- Racial, ethnic minorities often don’t practice sun-protective behaviors.
- Sunscreen regulations and advice for your patients.
Join us on Tuesday, October 8, 2019, at 8:00 pm EST on Twitter at #MDedgeChats as we discuss skin cancer, and what’s new in sunscreen, skin of color, and melanoma.
Special guests include physicians with expertise in dermatology and skin cancer, Anthony Rossi, MD (@DrAnthonyRossi), Julie Amthor Croley, MD, 15k followers on IG (@Drskinandsmiles), and Candrice Heath, MD (@DrCandriceHeath). Background information about the chat can be found below.
What will the conversation cover?
Q1: What are the most common types of skin cancer?
Q2: What recent research findings can better inform patients about skin cancer risks?
Q3: What’s the difference between melanoma in fair skin vs. darker skin?
Q4: How does the risk of skin cancer differ in people with darker skin?
Q5: Why should sunscreen be used even in the fall and winter?
Follow us here: @MDedgeDerm | @MDedgeTweets | #MDedgeChats
About Dr. Rossi:
Dr. Anthony Rossi (@DrAnthonyRossi) is a board-certified dermatologist with fellowship training in Mohs micrographic surgery, cosmetic and laser surgery, and advanced cutaneous oncology at the Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College program, both in New York. He specializes in skin cancer surgery, cosmetic dermatologic surgery, and laser surgery.
His research includes quality of life in cancer survivors, the use of noninvasive imaging of the skin, and nonsurgical treatments of skin cancer. Additionally, Dr. Rossi is active in dermatologic organizations and advocacy for medicine.
Research and Publications by Dr. Rossi
About Dr. Heath:
Dr. Candrice Heath (@DrCandriceHeath) is Assistant Professor of Dermatology at the Lewis Katz School of Medicine at Temple University in Philadelphia, Pennsylvania with fellowship training in pediatric dermatology at Johns Hopkins University in Baltimore, Maryland. Dr. Heath is triple board certified in pediatrics, dermatology, and pediatric dermatology. She specializes in adult and pediatric dermatology, skin of color, acne, and eczema. Dr. Heath also enjoys educating primary care physicians on the front lines of health care and delivering easy to understand information to consumers.
Research and publications by Dr. Heath
Guest host of MDedge podcast: A sunscreen update with Dr. Vincent DeLeo.
About Dr. Croley:
Dr. Julie Amthor Croley (@Drskinandsmiles) also known as “Dr. Skin and Smiles” has 15,000 followers on Instagram, and is a Chief Dermatology Resident at the University of Texas Medical Branch in Galveston, Texas. She has a special interest in skin cancer and dermatological surgery and hopes to complete a fellowship in Mohs micrographic surgery after residency. In her free time, Dr. Croley enjoys spending time with her husband (an orthopedic surgeon), running and competing in marathons, and spending time on the beach.
Cutaneous melanoma is the most fatal form of skin cancer and is a considerable public health concern in the United States. Early detection and management of skin cancer can lead to decreased morbidity and mortality from skin cancer. As a result, the American Academy of Dermatology Association supports safe sun-protective practices and diligent self-screening for changing lesions.
Sunscreen use is an essential component of sun protection. New regulations from the US Food and Drug Administration (FDA) have left consumers concerned about the safety of sunscreens. According to a recent Cutis editorial from Vincent A. DeLeo, MD, “There is no question that, as physicians, we want to ‘first, do no harm,’ so we should all be interested in assuring our patients that our sunscreen recommendations are safe and we support the FDA proposal for additional data.”
Patients with skin of color experience disproportionately higher morbidity and mortality when diagnosed with melanoma. “Poor prognosis in patients with skin of color is multifactorial and may be due to poor use of sun protection, misconceptions about melanoma risk, atypical clinical presentation, impaired access to care, and delay in diagnosis,” according to a recent Cutis article.
Population-based skin cancer screening performed exclusively by dermatologists is not practical. Primary care physicians and other experts in melanoma and public health need to be involved in reducing melanoma mortality.
In this chat, we will provide expert recommendations on the diagnosis of skin cancer, preventive measures, and the latest research discussed among physicians.
- “Doctor, Do I Need a Skin Check?”
- Assessing the effectiveness of knowledge-based interventions in skin of color populations.
- Melanoma in US Hispanics
- Podcast: Sunscreen update from Dr. Vincent DeLeo
- Windshield and UV exposure
- Racial, ethnic minorities often don’t practice sun-protective behaviors.
- Sunscreen regulations and advice for your patients.
Long-term opioid use more common in hidradenitis suppurativa
, in a retrospective cohort study.
“These results suggest that periodic assessment of pain and screening for long-term opioid use may be warranted, particularly among patients who are older, who smoke tobacco, or who have depression and other medical comorbidities,” wrote the authors of the study (JAMA Dermatol. 2019 Sep 11. doi: 10.1001/jamadermatol.2019.2610).
Researchers led by Sarah Reddy, BA, of the Zucker School of Medicine at Hofstra/ Northwell, New Hyde Park, N.Y., used data from a health-care database that represents an estimated 17% of the U.S. population. They focused on opioid-naive adults who were in the database for at least 3 years from 2008-2018 and monitored whether they began opioid use and then maintained use for at least 1 year.
Nearly 829,000 patients were in the control group, and 22,277 were in the HS group. The mean age of those with HS was 41 years, 76% were women, and 59% were white.
Over 1 year, the crude incidence of long-term opioid use among HS patients who were opioid naive was 0.33%, compared with 0.14% of controls (P less than .001).
An analysis, adjusted for potential confounding factors, found that compared with controls, those with HS were more likely to develop long-term opioid use (odds ratio [OR], 1.53, 95% confidence interval, 1.20-1.95; P less than .001). In the adjusted analysis, long-term opioid use was increased among those in the HS group who had ever smoked tobacco (OR, 3.64, 95% CI, 2.06-6.41; P less than .001), compared with patients with HS who had never smoked; and those who had a history of depression (OR, 1.97, 95% CI, 1.21-3.19; P = .006), compared with HS patients who had not had depression.
The risk of long-term opioid use among those with HS increased by 2% with each additional year in age.
In addition, 5% of patients with HS and long-term opioid use were diagnosed with opioid use disorder over the study period. “Sex, race/ethnicity, disease duration, established dermatologic care, alcohol abuse, and nonopioid substance abuse were not associated with increased risk of long-term opioid use among patients with HS,” the authors wrote.
Emphasizing that these results “should not further stigmatize” people with HS, they said, “our hope is that the medical community, including dermatologists, will further embrace and engage in an integrated care plan that comprehensively supports the needs of patients with HS, including pain management.”
Future research, they added, “should include evaluating the association between disease severity and risk of opioid use, the role of disease-modifying therapies in reducing opioid use, and the development of effective and appropriate multimodal pain management strategies for HS.”
An educational grant to a study author from AbbVie partially funded the study. No other study funding was reported. Ms. Reddy had no disclosures; one author disclosed having received grants and personal fees from AbbVie and UCB during the study.
SOURCE: Reddy S et al. JAMA Dermatol. 2019 Sep 11. doi: 10.1001/jamadermatol.2019.2610.
, in a retrospective cohort study.
“These results suggest that periodic assessment of pain and screening for long-term opioid use may be warranted, particularly among patients who are older, who smoke tobacco, or who have depression and other medical comorbidities,” wrote the authors of the study (JAMA Dermatol. 2019 Sep 11. doi: 10.1001/jamadermatol.2019.2610).
Researchers led by Sarah Reddy, BA, of the Zucker School of Medicine at Hofstra/ Northwell, New Hyde Park, N.Y., used data from a health-care database that represents an estimated 17% of the U.S. population. They focused on opioid-naive adults who were in the database for at least 3 years from 2008-2018 and monitored whether they began opioid use and then maintained use for at least 1 year.
Nearly 829,000 patients were in the control group, and 22,277 were in the HS group. The mean age of those with HS was 41 years, 76% were women, and 59% were white.
Over 1 year, the crude incidence of long-term opioid use among HS patients who were opioid naive was 0.33%, compared with 0.14% of controls (P less than .001).
An analysis, adjusted for potential confounding factors, found that compared with controls, those with HS were more likely to develop long-term opioid use (odds ratio [OR], 1.53, 95% confidence interval, 1.20-1.95; P less than .001). In the adjusted analysis, long-term opioid use was increased among those in the HS group who had ever smoked tobacco (OR, 3.64, 95% CI, 2.06-6.41; P less than .001), compared with patients with HS who had never smoked; and those who had a history of depression (OR, 1.97, 95% CI, 1.21-3.19; P = .006), compared with HS patients who had not had depression.
The risk of long-term opioid use among those with HS increased by 2% with each additional year in age.
In addition, 5% of patients with HS and long-term opioid use were diagnosed with opioid use disorder over the study period. “Sex, race/ethnicity, disease duration, established dermatologic care, alcohol abuse, and nonopioid substance abuse were not associated with increased risk of long-term opioid use among patients with HS,” the authors wrote.
Emphasizing that these results “should not further stigmatize” people with HS, they said, “our hope is that the medical community, including dermatologists, will further embrace and engage in an integrated care plan that comprehensively supports the needs of patients with HS, including pain management.”
Future research, they added, “should include evaluating the association between disease severity and risk of opioid use, the role of disease-modifying therapies in reducing opioid use, and the development of effective and appropriate multimodal pain management strategies for HS.”
An educational grant to a study author from AbbVie partially funded the study. No other study funding was reported. Ms. Reddy had no disclosures; one author disclosed having received grants and personal fees from AbbVie and UCB during the study.
SOURCE: Reddy S et al. JAMA Dermatol. 2019 Sep 11. doi: 10.1001/jamadermatol.2019.2610.
, in a retrospective cohort study.
“These results suggest that periodic assessment of pain and screening for long-term opioid use may be warranted, particularly among patients who are older, who smoke tobacco, or who have depression and other medical comorbidities,” wrote the authors of the study (JAMA Dermatol. 2019 Sep 11. doi: 10.1001/jamadermatol.2019.2610).
Researchers led by Sarah Reddy, BA, of the Zucker School of Medicine at Hofstra/ Northwell, New Hyde Park, N.Y., used data from a health-care database that represents an estimated 17% of the U.S. population. They focused on opioid-naive adults who were in the database for at least 3 years from 2008-2018 and monitored whether they began opioid use and then maintained use for at least 1 year.
Nearly 829,000 patients were in the control group, and 22,277 were in the HS group. The mean age of those with HS was 41 years, 76% were women, and 59% were white.
Over 1 year, the crude incidence of long-term opioid use among HS patients who were opioid naive was 0.33%, compared with 0.14% of controls (P less than .001).
An analysis, adjusted for potential confounding factors, found that compared with controls, those with HS were more likely to develop long-term opioid use (odds ratio [OR], 1.53, 95% confidence interval, 1.20-1.95; P less than .001). In the adjusted analysis, long-term opioid use was increased among those in the HS group who had ever smoked tobacco (OR, 3.64, 95% CI, 2.06-6.41; P less than .001), compared with patients with HS who had never smoked; and those who had a history of depression (OR, 1.97, 95% CI, 1.21-3.19; P = .006), compared with HS patients who had not had depression.
The risk of long-term opioid use among those with HS increased by 2% with each additional year in age.
In addition, 5% of patients with HS and long-term opioid use were diagnosed with opioid use disorder over the study period. “Sex, race/ethnicity, disease duration, established dermatologic care, alcohol abuse, and nonopioid substance abuse were not associated with increased risk of long-term opioid use among patients with HS,” the authors wrote.
Emphasizing that these results “should not further stigmatize” people with HS, they said, “our hope is that the medical community, including dermatologists, will further embrace and engage in an integrated care plan that comprehensively supports the needs of patients with HS, including pain management.”
Future research, they added, “should include evaluating the association between disease severity and risk of opioid use, the role of disease-modifying therapies in reducing opioid use, and the development of effective and appropriate multimodal pain management strategies for HS.”
An educational grant to a study author from AbbVie partially funded the study. No other study funding was reported. Ms. Reddy had no disclosures; one author disclosed having received grants and personal fees from AbbVie and UCB during the study.
SOURCE: Reddy S et al. JAMA Dermatol. 2019 Sep 11. doi: 10.1001/jamadermatol.2019.2610.
FROM JAMA DERMATOLOGY
Heart disease raises risk of severe cutaneous adverse reactions to allopurinol
Researchers have found that patients with heart disease have an increased risk of hospitalization for severe cutaneous adverse reactions to allopurinol, with factors like chronic kidney disease and high initial dosage adding to that risk.
“Physicians who prescribe allopurinol should look for these risk factors so that they may consider initiating lower-dosage allopurinol and other precautions, which may prevent this rare but serious adverse reaction,” Chio Yokose, MD, of Massachusetts General Hospital in Boston and coauthors wrote in the Canadian Medical Association Journal.
To further investigate known associations between heart disease and severe cutaneous adverse reactions to allopurinol – including Stevens-Johnson syndrome and toxic epidermal necrolysis – the researchers used an administrative database known as Population Data BC to conduct a cohort study of allopurinol initiators in British Columbia between 1997 and 2015. Individuals with a history of severe cutaneous adverse reactions before starting allopurinol were excluded.
Of the 130,325 allopurinol users identified, 109 were hospitalized for allopurinol-associated severe cutaneous adverse reactions within 3 months of starting the drug. One in 655 allopurinol users with heart disease were admitted to the hospital for allopurinol-associated severe cutaneous adverse reaction (risk ratio = 1.53 per 1,000; 95% confidence interval, 1.10-2.06), compared with 1 in 1,548 allopurinol users without heart disease (risk ratio = 0.65 per 1,000; 95% CI, 0.50-0.82).
After multivariable analysis, other significant associations with hospital admission included chronic kidney disease (relative risk, 1.88; 95% CI, 1.17-3.02) and an initial allopurinol dosage greater than 100 mg/day (RR, 2.78; 95% CI, 1.75-4.43). In addition, patients with heart disease, chronic kidney disease, and an initial dosage greater than 100 mg/day had an 11-fold higher risk of hospital admission (RR, 11.13; 95% CI, 4.66-26.58).
The authors acknowledged their study’s limitations, including potential misclassification of reactions and comorbidities that can stem from a reliance on ICD codes. However, they also noted that “any misclassification is expected to be nondifferential” and bias results toward the null accordingly.
The study was funded by the Canadian Institutes of Health Research. One author reported receiving a grant from the National Institutes of Health and research support from AstraZeneca, along with consulting fees from Takeda, Selecta Biosciences, and Horizon. No other conflicts of interest were reported.
SOURCE: Yokose C et al. CMAJ. 2019 Sep 30. doi: 10.1503/cmaj.190339.
Researchers have found that patients with heart disease have an increased risk of hospitalization for severe cutaneous adverse reactions to allopurinol, with factors like chronic kidney disease and high initial dosage adding to that risk.
“Physicians who prescribe allopurinol should look for these risk factors so that they may consider initiating lower-dosage allopurinol and other precautions, which may prevent this rare but serious adverse reaction,” Chio Yokose, MD, of Massachusetts General Hospital in Boston and coauthors wrote in the Canadian Medical Association Journal.
To further investigate known associations between heart disease and severe cutaneous adverse reactions to allopurinol – including Stevens-Johnson syndrome and toxic epidermal necrolysis – the researchers used an administrative database known as Population Data BC to conduct a cohort study of allopurinol initiators in British Columbia between 1997 and 2015. Individuals with a history of severe cutaneous adverse reactions before starting allopurinol were excluded.
Of the 130,325 allopurinol users identified, 109 were hospitalized for allopurinol-associated severe cutaneous adverse reactions within 3 months of starting the drug. One in 655 allopurinol users with heart disease were admitted to the hospital for allopurinol-associated severe cutaneous adverse reaction (risk ratio = 1.53 per 1,000; 95% confidence interval, 1.10-2.06), compared with 1 in 1,548 allopurinol users without heart disease (risk ratio = 0.65 per 1,000; 95% CI, 0.50-0.82).
After multivariable analysis, other significant associations with hospital admission included chronic kidney disease (relative risk, 1.88; 95% CI, 1.17-3.02) and an initial allopurinol dosage greater than 100 mg/day (RR, 2.78; 95% CI, 1.75-4.43). In addition, patients with heart disease, chronic kidney disease, and an initial dosage greater than 100 mg/day had an 11-fold higher risk of hospital admission (RR, 11.13; 95% CI, 4.66-26.58).
The authors acknowledged their study’s limitations, including potential misclassification of reactions and comorbidities that can stem from a reliance on ICD codes. However, they also noted that “any misclassification is expected to be nondifferential” and bias results toward the null accordingly.
The study was funded by the Canadian Institutes of Health Research. One author reported receiving a grant from the National Institutes of Health and research support from AstraZeneca, along with consulting fees from Takeda, Selecta Biosciences, and Horizon. No other conflicts of interest were reported.
SOURCE: Yokose C et al. CMAJ. 2019 Sep 30. doi: 10.1503/cmaj.190339.
Researchers have found that patients with heart disease have an increased risk of hospitalization for severe cutaneous adverse reactions to allopurinol, with factors like chronic kidney disease and high initial dosage adding to that risk.
“Physicians who prescribe allopurinol should look for these risk factors so that they may consider initiating lower-dosage allopurinol and other precautions, which may prevent this rare but serious adverse reaction,” Chio Yokose, MD, of Massachusetts General Hospital in Boston and coauthors wrote in the Canadian Medical Association Journal.
To further investigate known associations between heart disease and severe cutaneous adverse reactions to allopurinol – including Stevens-Johnson syndrome and toxic epidermal necrolysis – the researchers used an administrative database known as Population Data BC to conduct a cohort study of allopurinol initiators in British Columbia between 1997 and 2015. Individuals with a history of severe cutaneous adverse reactions before starting allopurinol were excluded.
Of the 130,325 allopurinol users identified, 109 were hospitalized for allopurinol-associated severe cutaneous adverse reactions within 3 months of starting the drug. One in 655 allopurinol users with heart disease were admitted to the hospital for allopurinol-associated severe cutaneous adverse reaction (risk ratio = 1.53 per 1,000; 95% confidence interval, 1.10-2.06), compared with 1 in 1,548 allopurinol users without heart disease (risk ratio = 0.65 per 1,000; 95% CI, 0.50-0.82).
After multivariable analysis, other significant associations with hospital admission included chronic kidney disease (relative risk, 1.88; 95% CI, 1.17-3.02) and an initial allopurinol dosage greater than 100 mg/day (RR, 2.78; 95% CI, 1.75-4.43). In addition, patients with heart disease, chronic kidney disease, and an initial dosage greater than 100 mg/day had an 11-fold higher risk of hospital admission (RR, 11.13; 95% CI, 4.66-26.58).
The authors acknowledged their study’s limitations, including potential misclassification of reactions and comorbidities that can stem from a reliance on ICD codes. However, they also noted that “any misclassification is expected to be nondifferential” and bias results toward the null accordingly.
The study was funded by the Canadian Institutes of Health Research. One author reported receiving a grant from the National Institutes of Health and research support from AstraZeneca, along with consulting fees from Takeda, Selecta Biosciences, and Horizon. No other conflicts of interest were reported.
SOURCE: Yokose C et al. CMAJ. 2019 Sep 30. doi: 10.1503/cmaj.190339.
FROM THE CANADIAN MEDICAL ASSOCIATION JOURNAL
Beyond the lips: Guidance for intraoral procedures
NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.
Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.
An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.
On the labial mucosa, an elliptical incision is often a good choice.
Cutaneous lip procedures
On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.
Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
Gingival and tongue procedures
Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.
Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.
For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
Considerations in biopsy technique
Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.
“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.
Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”
When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.
Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.
Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
Salivary gland biopsies and intraoral suturing
Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.
First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”
Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.
If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.
Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
Postoperative care, complications, and the limits of the dermatologist
Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.
As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.
Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.
When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.
NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.
Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.
An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.
On the labial mucosa, an elliptical incision is often a good choice.
Cutaneous lip procedures
On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.
Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
Gingival and tongue procedures
Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.
Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.
For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
Considerations in biopsy technique
Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.
“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.
Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”
When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.
Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.
Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
Salivary gland biopsies and intraoral suturing
Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.
First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”
Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.
If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.
Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
Postoperative care, complications, and the limits of the dermatologist
Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.
As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.
Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.
When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.
NEW YORK –The work of the dermatologist doesn’t need to stop at the lips, according to Nasim Fazel, MD, DDS, a board-certified dermatologist and dentist. she said, speaking at a session focused on oral health and procedures at the American Academy of Dermatology summer meeting.
Whether to perform an incisional or excisional biopsy on the lips or within the oral cavity is a decision driven by the clinical scenario, said Dr. Fazel, professor of clinical dermatology and director of the oral mucosal disease clinic at the University of California, Davis. Variables to consider, she said, include the size of the lesion, as well as whether the lesion is symptomatic or there’s any functional impairment. Other factors to bear in mind are whether the patient has any comorbid inflammatory conditions and whether the lesion could be malignant.
An excisional biopsy is a good procedure for small lesions that are thought to be benign, especially if they are exophytic, she noted. An example would be a traumatic fibroma, she said. This technique is also appropriate if there’s concern for dysplasia or malignancy if an office excisional biopsy is feasible given lesion size and location.
On the labial mucosa, an elliptical incision is often a good choice.
Cutaneous lip procedures
On the cutaneous lip, a punch incision can be feasible. The vermilion border should be marked to maintain orientation. “Avoid transecting the vermilion border to the extent that it’s possible,” said Dr. Fazel. Keep the vascular anatomy in mind as well, she added, since there’s a risk of severing the superior or inferior labial artery with procedures in this area. If this should happen, the branch can be identified and ligated with 4-0 fast gut or chromic gut suture material, she advised.
Another option on the cutaneous lip is shave removal. Here, a chalazion clamp can be used for both exposure and hemostasis. “Always suture parallel to the lip lines, and caution the patient that there may be significant, noticeable blanching when lip anesthesia’s used,” she said.
Gingival and tongue procedures
Moving to territory that may be less familiar for some dermatologists, Dr. Fazel walked through the process of a gingival punch biopsy. “Use local anesthetic, but a small quantity is sufficient,” she said. Using gentle pressure, the operator can work the punch instrument down to periosteal bone. At that point, just scissors can be used for undermining the specimen, with minimal disturbance of the mucosal surface.
Hemostasis after a gingival punch can be accomplished with silver nitrate or aluminum chloride or by electrocautery. A permanent defect in the gingiva can occur even with good technique, she said – a fact that should be included in the informed consent document for the procedure.
For lesions on the tongue, a shave removal can be considered, as can an incisional punch biopsy. An assistant’s hands are invaluable for stabilizing the tongue, said Dr. Fazel, illustrating that small dry gauze squares help achieve a good grip.
Considerations in biopsy technique
Dr. Fazel offered some tips and considerations when a punch biopsy is being done in the context of a chronic oral inflammatory condition, and the plan is to submit for hematoxylin and eosin (H&E) staining and direct immunofluorescence (DIF). Conditions where an intraoral punch biopsy would be considered include bullous or mucous membrane pemphigoid, pemphigus, lichen planus, and systemic lupus erythematosus, she said.
“Select a site with the most significant inflammatory changes” and aim for the most anterior site that exhibits these characteristics to maximize exposure and ensure a good specimen. The labial mucosa is a better choice in general than buccal mucosa, she said. “Maxillary and mandibular sulci are tricky sites,” especially when perilesional and lesional tissue should be included in the biopsies.
Next, Dr. Fazel walked attendees through general principles of preparing for and performing punch biopsies for H&E and DIF. In planning the biopsies, the DIF specimen should ideally be collected before the H&E specimen because the former technique will have higher yield when the specimen is taken from a less bloody field. “The yield of DIF is higher from the gingiva than from nonkeratinized surfaces.”
When infiltrating the biopsy site with local anesthesia, the needle should be centered within the lesion or general area to be biopsied, and care should be taken to maintain the orientation of the lesion to the surrounding tissue. Anesthesia can be infiltrated within the submucosal plane; the resultant ballooning will elevate the tissue to be biopsied and ease the procedure, she said.
Choose a 3-mm punch tool for gingival biopsies; 4 mm is a good size for other nonkeratinized surfaces. Unlike the procedure used for cutaneous biopsies, on delicate oral tissues, “you don’t need to hub your punch tool,” Dr. Fazel said. Similarly, the tool can be driven with firm rotation in one direction, rather than ratcheting back and forth, which may fray and deform the biopsy margins, she added. The specimen can be freed from surrounding mucosa with scissors alone and a gentle snipping motion; everting the tissue will help achieve the desired clean and gentle technique.
Because of the delicacy of the tissue, “it’s important to minimize the use of forceps, as well as any unnecessary manipulation of tissue in the process of specimen collection,” she said.
Salivary gland biopsies and intraoral suturing
Even minor salivary glands can be biopsied in a fairly straightforward way, though there’s a risk of short- and long-term loss of sensation, as well as more scarring than in other routine intraoral biopsies. Though these salivary glands lie just beneath the oral mucosa, care must be taken to avoid laceration of the orbicularis oris muscle during excision, noted Dr. Fazel. With a minor salivary gland biopsy, as with some other intraoral procedures, sutures will be needed. Consideration for the friability of the oral mucosa should drive suture material choice and closure technique.
First, “take bigger bites on each side of the incision, to minimize the risk of the suture tearing through the mucosa,” she said. Avoid forceps while suturing if possible, but be gentle if they are employed, “and be gentle tying knots: retract the mucosa as little as possible and cinch the knots down tightly with your fingers.”
Electrocautery, silver nitrate, and aluminum chloride are all reasonable options for hemostasis, although patients should be alerted that the tissue will have a charred appearance if electrocautery is used. Primary closure may be all that’s needed for hemostasis, said Dr. Fazel.
If nonabsorbable suture materials are used, nylon and prolene should be avoided since they tend to tear through the oral mucosa. Soft or braided silk are good choices, she said, and sutures can come out in 5-7 days.
Absorbable sutures have the advantage of not requiring removal, but they can be more irritating to the surrounding mucosa. Chromic or fast gut are the choices here, said Dr. Fazel. Whether absorbable or nonabsorbable sutures are placed, the size should be 4-0 or 5-0, she said.
Postoperative care, complications, and the limits of the dermatologist
Postoperatively, patients should know that swelling is to be expected, especially with procedures like minor salivary gland biopsies that involve the lip. Icing 15 minutes per hour for the first few hours will help with swelling; wound care is optimized with gentle salt water rinses. A bland diet that avoids acidic, spicy, and excessively hot foods and beverages will minimize wound irritation. Foods with sharp edges like chips, crackers, and nuts can actually catch sutures and cause pain and bleeding, so these too should be avoided.
As with dental work, care should be taken with eating or drinking until anesthesia has worn off, which may take up to 3 hours. Patients should also be cautioned that sutures are likely to come out prematurely just because of the mobility of the structures of the mouth with normal activities such as eating and talking.
Should a wound infection occur, said Dr. Fazel, it’s likely that mixed aerobic and anaerobic bacteria are to blame; accordingly, broad-spectrum beta-lactam antibiotics can be a good first-line course. More severe infections are more likely to have an anaerobic or gram-negative etiology; metronidazole is a reasonable choice for anaerobic coverage, she noted. The life-threatening complication not to miss is cellulitis of the floor of the mouth, or Ludwig angina. The swelling results in superior and posterior displacement of the tongue, obstructing the upper airway, so any patient suspected of having Ludwig angina needs emergent evaluation and treatment.
When should a dermatologist consider referral to an otolaryngologist rather than diving into a biopsy in the dermatology clinic? If the area of concern is on the posterior third of the tongue, access without special tools or higher levels of anesthesia becomes tricky, Dr. Fazel pointed out. The posterior hard palate, the soft palate, and the floor of the mouth are also regions best left to otolaryngologists, she said.
EXPERT ANALYSIS SUMMER AAD 2019
Study aims to define symptoms of Sjögren’s syndrome secondary to SLE
Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.
Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.
“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”
The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.
The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).
“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”
They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.
The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.
SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.
Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.
Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.
“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”
The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.
The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).
“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”
They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.
The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.
SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.
Sjögren’s syndrome secondary to systemic lupus erythematosus rises in frequency with age, affects nearly one-quarter of all people with SLE, and is marked by a systemic inflammatory state with high levels of proinflammatory cytokines.
Those are key findings from a Swedish study that set out to evaluate the subjective and objective symptoms of secondary Sjögren’s syndrome (sSS) from a large cohort of SLE patients and matched controls.
“The diagnosis SS is a clinical entity, based on dryness of eyes and mouth due to destructive inflammation in the exocrine glands, especially tear and salivary glands,” researchers led by Guillermo Ruacho, DMD, and Marika Kvarnström, MD, PhD, of the Karolinska Institute, wrote in a study published in the Journal of Rheumatology (doi: 10.3899/jrheum.190250). “SS can exist [as] isolated, primary SS (pSS) or together with other rheumatic diseases, referred to as secondary SS (sSS). A major difference according to the 2002 Revised American-European Consensus Criteria (AECC) is the classification where the serologic item (SSA/SSB antibodies) is included for pSS, but not for sSS (Ann Rheum Dis. 2002;61:554-8). In SLE, these autoantibodies are common, usually stable over time, and they appear early, even several years before disease onset.”
The researchers evaluated 504 consecutive SLE patients and 319 controls from the general population, who were matched for age and gender to the first 319 SLE patients. They used AECC to define SLE-sSS and conducted a thorough clinical investigation of all patients, including analysis of autoantibodies and 20 selected cytokines.
The researchers found that SLE-sSS occurred in 23% of the SLE patients. In comparison with SLE patients who did not have sSS, those in the SLE-sSS group were an average of 9 years older, more likely to be female (96% vs. 84%, respectively), and more likely to have leukopenia (57% vs. 45%), yet less likely to have nephritis (32% vs. 43%). Of 20 proinflammatory cytokines investigated, 6 were higher in the SLE-sSS group: TNF-alpha, IL-6, MCP-4, MIP-1beta, IL-12/IL-23p40, and IP-10. Other clinical measures higher in the SLE-sSS group were total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA; P less than .05 for all comparisons).
“To our knowledge this is the first study to investigate if systemic inflammation, as measured by cytokine levels, differs between SLE-sSS and SLE-nonsSS,” the researchers wrote. “In clinical practice, it is often difficult to delineate pSS from SLE-sSS. Organ manifestations commonly reported in pSS are fever, lymphadenopathy, parotid gland enlargement, Raynaud’s phenomenon, interstitial lung disease, peripheral neuropathy, and vasculitis. All these clinical features, except parotid gland enlargement, were investigated in the present study, but only peripheral neuropathy differed and was more frequent in SLE-sSS than in SLE-nonsSS.”
They acknowledged certain limitations of the study, including the fact that they did not measure saliva and tear production in controls without sicca symptoms.
The study was supported by funds from Swedish local and national governments, medical societies, foundations, and patient advocacy groups, One author is an employee at AstraZeneca, which provided reagents for the cytokine analyses but had no impact on the analyses, the authors said.
SOURCE: Ruacho G et al. J Rheumatol. 2019 Sep 1. doi: 10.3899/jrheum.190250.
FROM THE JOURNAL OF RHEUMATOLOGY